Molecular, Clinical Features, and Prognostic Implications of PTPN11 Mutation in Adult Patients with Acute Myeloid Leukemia in China.

Background: Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic mutations and chromosomal abnormalities that significantly influence disease progression and outcomes. While PTPN11 mutations have been extensively studied in pediatric leukemia, their clinical significance in adult AML, particularly in the Chinese population where they exhibit a relatively rare prevalence, remains poorly understood.

Methods: This retrospective single-center study analyzed 22 adult AML patients with PTPN11 mutations diagnosed between 2018 and 2023. Next-generation sequencing (NGS) was performed to detect PTPN11 and other AML-associated gene mutations, while cytogenetic risk stratification followed the European Leukemia Net (ELN) 2022 guidelines. Kaplan-Meier survival analysis and Cox regression were used to assess prognostic factors, with a focus on overall survival (OS) and event-free survival (EFS).

Results: Among the 22 patients with PTPN11 mutations, 27% also harbored FLT3-ITD mutations. Patients with FLT3-ITD mutations had significantly lower platelet counts (p = 0.02) and higher albumin levels (p = 0.039) com-pared to FLT3-ITD wild-type patients. The most common co-occurring mutations in PTPN11-positive patients were NPM1 (45.5%) and DNMT3A (36.4%). Survival analysis revealed that FLT3-ITD mutations were associated with poorer OS and EFS, while NPM1 mutations predicted better outcomes. Importantly, the prognostic impact of PTPN11 appeared to depend on co-occurring mutations, with NPM1 mitigating the adverse effects of FLT3-ITD.

Conclusions: This study highlights the molecular and clinical heterogeneity of PTPN11 mutations in AML, emphasizing their prognostic complexity and the need for integrated molecular profiling. These findings provide valuable insights into the role of PTPN11 mutations and underscore the importance of personalized treatment approaches based on genetic risk stratification.